Buchwald–Hartwig amination: 4-(4-Bromobenzyl)morpholine → 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine
0% yield, run at 90 °C, as recorded by experimental reaction archive. The written procedure is below. One of 4 recorded runs making this product; all of them are compared below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | 4-(4-Bromobenzyl)morpholine | C₁₁H₁₄BrNO | |
| Reactant | 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine | C₁₃H₁₆FN₅O | |
| Reagent | Sodium 2-methylbutan-2-olate | C₅H₁₁NaO | |
| Catalyst | (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)- | C₃₂H₆₂FeP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,2-Dimethoxyethane | C₄H₁₀O₂ | |
| Product | 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine | C₂₄H₂₉FN₆O₂ | 0% |
Conditions
- Temperature
- 90 °C
Yield
- 0% of 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-N-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine.
Every recorded run making this product
4 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 100 °C | — | 86% |
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Sodium 2-methylbutan-2-olate | Toluene | 110 °C | — | 6% |
| 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl; Bis(dibenzylideneacetone)palladium | Sodium 2-methylbutan-2-olate | Butyl Acetate | 100 °C | — | 0% |
| (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)-; Palladium (II) acetate | Sodium 2-methylbutan-2-olate | 1,2-Dimethoxyethane | 90 °C | — | 0% (this run) |
Procedure
Copied from the source record, unedited
The aim of the reaction is only optimization and test. The reaction described below was carried out under argon atmosphere. Palladium(II) acetate (2.245 mg, 10.00 µmol) and (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (5.61 mg, 10.00 µmol) were mixed in DME (0.2 mL) in a 1.4 ml vial under argon and stirred for 1 minute at room temperature. The orange pre-mixed Pd-catalyst solution were added to a 10 mL Schlenk-tube containing 4-(4-bromobenzyl)morpholine (0.282 g, 1.1 mmol) and Sodium tert- pentoxide (0.161 g, 1.46 mmol) in DME (1.5 mL). Finally, 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (0.277 g, 1 mmol) was added and the bright orange reaction mixture was stirred at 90 °C. The mixture turned from bright orange in
The source
This record comes from experimental reaction archive (ord-bd19c64fd71c4dc0a1f39c0c85d4d230). Open the source and check it against what is on this page.
experimental reaction archive record ord-bd19c64fd71c4dc0a1f39c0c85d4d230 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.
How to read this record
This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.
The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.
Where to next
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